A randomized phase III trial of dexamethasone mouthwash to prevent chemotherapy-induced oral mucositis in patients with breast cancer.

12017 Background: Oral mucositis is a common adverse event in patients undergoing chemotherapy for breast cancer. A previous randomized phase II trial showed that a dexamethasone-based mouthwash significantly reduced the incidence and severity of chemotherapy-induced oral mucositis. The SMASH-BC trial was designed to confirm the efficacy and safety of dexamethasone-based mouthwash for preventing chemotherapy-induced oral mucositis in patients with breast cancer. Methods: This multicenter, open-label, randomized phase III trial was conducted in Japan. Patients with early breast cancer scheduled to receive standard adjuvant or neoadjuvant chemotherapy (AC, EC, dose-dense AC/EC, TC, or pembrolizumab-containing regimens) were randomized 1:1 to receive either a dexamethasone-based mouthwash (10 mL of dexamethasone elixir 0.01%) or tap-water mouthwash as a control. The mouthwash was swished for 2 min and spit, four times daily for 8 weeks, starting on day 1 of chemotherapy. Randomization was stratified by chemotherapy regimen, smoking status, and institution. The primary endpoint was the incidence of all-grade oral mucositis at 8 weeks, assessed using electronic patient-reported outcomes (ePRO). Assuming an all-grade oral mucositis incidence of 55% in the control group and 35% in the intervention group, 212 patients were required to provide 80% power with a two-sided α of 0.05. The planned sample size was 230, allowing for 10% attrition. Results: Overall, 230 patients were randomized (intervention, n = 117; control, n = 113), and 220 patients (intervention, n = 114; control, n = 106) were included in the analysis. The incidence of ePRO-assessed all-grade oral mucositis at 8 weeks was 58.8% and 63.2% in the intervention and control groups, respectively (risk ratio [RR], 0.93; 95% confidence interval [CI], 0.75–1.15; P = 0.59). The incidence of ePRO-assessed moderate-to-very severe oral mucositis was 13.2% and 18.9% in the intervention and control groups, respectively (RR, 0.70; 95% CI, 0.38–1.29). During the 56-day study period, mucositis reported by ePRO on a median of 2 and 6 days in the intervention and control groups, respectively (median difference −4 days; 95% CI, −5.3 to 8.3 days). The incidence of physician-assessed oral mucositis was 31.9% vs. 41.5% in the intervention and control groups, respectively (RR, 0.77; 95% CI, 0.54–1.09). The incidence of grade ≥ 3 adverse events was 6.2% and 6.6% in the intervention and control groups, respectively (RR, 0.94; 95% CI, 0.34–2.58). However, the incidence of oral candidiasis was higher in the intervention group (5.4% vs 0%). Conclusions: Prophylactic dexamethasone mouthwash did not significantly reduce all-grade oral mucositis at 8 weeks. Overall safety was comparable between groups; however, the incidence of oral candidiasis was higher in the intervention group. Clinical trial information: jRCTs071240036.